The present invention relates to a system for monitoring of cell cultures, and in particular to a system of monitoring cell cultures using infrared sensors and cameras to detect changes in the pattern of heat production within metabolically active cells.
Cells are commonly grown in the lab on dishes or in wells that contain nutrients. These may be human or animal cells, as well as microorganisms such as bacteria, fungi and archaea used in research or clinical diagnostics and therapeutics. Cells are typically grown in an incubator with controlled temperature and humidity. To determine the degree of growth of cells, they are most often monitored visually by a human. For example, samples from potential infection sites in patients are inoculated on a Petri dish and a lab technician may visually inspect the dish after a few hours to a few days to spot signs of bacterial colony formation. This is labor intensive and also is associated with a risk for contamination. When cells require a strict anaerobic environment, visually inspecting them entails exposing them (even if for a limited period of time) to air, which may delay their growth or lead to their death. Visual inspection is widely used to determine bacterial susceptibility to antibiotics, for example using the disc-diffusion test, wherein bacterial growth is inhibited around a disc containing an antibiotic drug. However, it is practically impossible for humans to continuously monitor cells in culture. Moreover, for microorganism growth to be visually evident to the naked eye takes an extremely high number of cells to be accumulated.
Yet the ability to continuously monitor cells in culture is desirable. For example, it could shorten the time until an infection is diagnosed or the time needed to determine what the most effective antibiotic would be to treat a patient. Moreover, cells may stop growing or die due to lack of nutrients, unbalanced ambient conditions or infection by viruses, phages and fungi. Early detection of impaired cell growth is important in addressing the problem causing impaired growth. For example, early detection may allow for ambient conditions to be modified before cells experience irreversible damage. Early detection of an infection affecting cells may allow for control measures to be taken to prevent spread of the infection to other cells or specimens.
Continuous monitoring of the rate of cell growth may also be used to support research related to the use of medications. When medications or other interventions such as genetic modifications intended or potentially capable of cell growth or metabolism are investigated, continuous monitoring can quantify their effect on cells and provide a measure of the kinetics of their action. Impairment in cell growth or metabolic activity, or increased rate of cell growth may be adverse effects of drugs. Continuous monitoring of cell growth may allow for better detecting such effects.
With the advent of technology, cells are often cultured in small compartments such as wells, which are more difficult to visually inspect. Spectrometry is used to measure cell concentration in a liquid medium but this requires manually positioning of wells or other containers in a designated device which is not located within the incubator. This is labor intensive, increases the risk of mistakes and requires displacement of cells from their preferred culture environment, which may have adverse effects on cell growth. Automated agar plate inoculation systems exist that perform seeding of microbiologic samples on plates and monitor their growth using a camera but these do not use infrared cameras, and are not commonly used in the research setting due to their inflexibility and high price.